Human hepatoblast phenotype maintained by hyaluronan hydrogels.
Human hepatoblast phenotype maintained by hyaluronan hydrogels.
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DOI：
10.1002/jbm.b.30717
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
W. Turner;E. Schmelzer;R. McClelland;E. Wauthier;Weiliam Chen;L. Reid
中科院分区：
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作者：
W. Turner;E. Schmelzer;R. McClelland;E. Wauthier;Weiliam Chen;L. Reid
人成肝细胞和肝干细胞，产生肝细胞和胆管细胞的多能肝祖细胞，从胎肝中分离，并发现在新鲜分离的细胞和培养后表达透明质酸受体（CD 44）。这暗示了体内连接到透明质酸（HA），胚胎基质组分，作为用于肝祖细胞扩增和/或分化的候选三维（3-D）支架。为了评估HA作为支架，将成肝细胞和肝干细胞接种到HA水凝胶中，该水凝胶具有针对肝祖细胞扩增而定制的无血清、经组织确定的培养基。在HA水凝胶内形成细胞聚集体，并保持活力，增殖，并在超过4周的培养过程中表现出介于肝干细胞和成肝细胞之间的稳定表型，几乎没有证据表明对肝细胞或胆道途径的谱系限制。表型包括肝细胞和胆道标志物如胆汁特异性细胞角蛋白、CK 19、低水平白蛋白表达和尿素合成的稳定共表达。HA水凝胶是理想的多能肝祖细胞的3-D支架，并且应该可用于产生用于生物人工肝或组织工程肝移植物的细胞。
Human hepatoblasts and hepatic stem cells, pluripotent hepatic progenitors that give rise to hepatocytes and biliary cells, were isolated from fetal livers and found to express hyaluronan receptors (CD44) in both the freshly isolated cells and after culture. This implicates an in vivo connection to hyaluronan (HA), an embryonic matrix component, as a candidate 3-dimensional (3-D) scaffold for hepatic progenitor cell expansion and/or differentiation. To assess HAs as scaffolds, hepatoblasts and hepatic stem cells were seeded into HA hydrogels with a serum-free, hormonally defined medium tailored for expansion of hepatic progenitors. Cell aggregates formed within the HA hydrogels and remained viable, proliferative, and demonstrated a stable phenotype intermediate between that of hepatic stem cells and hepatoblasts throughout more than 4 weeks of culturing, with little evidence of lineage restriction towards either hepatocytic or biliary pathways. The phenotype consisted of stable co-expression of both hepatocytic and biliary markers such as biliary-specific cytokeratin, CK19, low levels of expression of albumin, and urea synthesis. HA hydrogels are ideal as 3-D scaffolds for pluripotent hepatic progenitors and should be useful for generating cells to be used in bioartificial livers or tissue engineered liver grafts.